[Role of kappa1 opioid receptors and cAMP in regulation of cardiac tolerance to ischemia and reperfusion].
Cardioprotective, inotropic, and antiarrhythmic effects of the selective agonist of k1-opioid receptors (k1-ORs) U-50.488H have been studied after 45-min global ischemia and 30-min reperfusion of isolated perfused rat hearts. The heart k1-ORs were stimulated by adding 0.1 or 1 mmol/l U-50.488H to the perfusion solution. The opioid did not affect the frequency of reperfusion arrhythmias. At a concentration of 0.1 mmol/l, it induced a twofold decrease in the reperfusion release of creatine phosphokinase (CPK), which positively correlated with a decrease in the myocardial cAMP level (r = 0.89, p < 0.01). Application of U-50.488H at a final concentration of 1 mmol/l did not change the cAMP level and CPK release. These results suggest that the cardioprotective effect of U-50.488H is due to a decrease in the level of cAMP in cardiomyocytes. Activation of k1-ORs decreased the frequency and force of myocardial contractions. It has been shown that the negative inotropic and chronotropic effects of U-50.488H are independent of changes in the myocardial cAMP level. A hypothesis is proposed that the absence of cardioprotective effect of 1 mM U-50.488H is a result of activation of nonopioid receptors in cardiomyocytes.
Lasukova
T V
TV
Maslov
L N
LN
Platonov
A A
AA
Guzarova
N V
NV
Lishmanov
Iu B
IuB
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001145:Arrhythmias, Cardiac / Q000188:drug therapy / Q000378:metabolism; D002316:Cardiotonic Agents / Q000494:pharmacology*; D003402:Creatine Kinase / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D008297:Male; D017202:Myocardial Ischemia / Q000188:drug therapy / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017473:Receptors, Opioid, kappa / Q000819:agonists* / Q000378:metabolism; D015424:Reperfusion
D000959:Antihypertensive Agents; D002316:Cardiotonic Agents; D017473:Receptors, Opioid, kappa; C116587:kappa(1) opioid receptor; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000242:Cyclic AMP; D003402:Creatine Kinase